Abstract The Flaviviruses, especially Dengue, Zika and Yellow Fever have been a major public health concern for centuries in semi and tropical climates, including parts of the southern US. Presently, these viruses are the cause of more than 300 million infections per year. Global travel, alteration of the underlying mosquito vector?s geographical range, the possibility of RNA genome mutation resulting from vector changes and new environmental selective pressures all appear to have influenced the spread of Flavivirus infection to new human populations. More recently, Zika, with the proposed link to microcephaly and other neurological birth defects, has thrust into the spotlight an urgent need for an economical, international-scale screening of susceptible populations. We believe there is a critical need to develop new technology to collect, transport and recover blood or blood products containing this pervasive class of unstable enveloped RNA virus, in the complete absence of any sort of protection via refrigeration. The goal of this new technology is the recovery of intact viral genomes to support viral load and nucleic acid testing: to improve the diagnoses of Flavivirus infection and, coupled with new, now- inexpensive methods of Next Gen sequencing, to provide the real possibility of discovering how the viral genome may be mutating under selective pressure. The overarching requirement for such new sample collection and preservation technology is that it must be robust enough to preserve even the most unstable of the Flavivirus RNAs, yet inexpensive enough to support both population scale public health screening and sophisticated molecular epidemiology to detect mutational drift (via Next-Gen sequencing) while being deployable in a way that facilitates implementation in isolated, tropical, poor, susceptible populations in the complete absence of cryogenic preservation. GenTegra, in collaboration with Ahlstrom (the world-leader in medical grade filter paper for newborn screening) have recently co-developed a medical grade cellulose paper that supports long term stabilization of the DNA in blood at ambient temperature. In this Phase II SBIR, GenTegra will leverage that ongoing collaboration with Ahlstrom, coupled with our expertise in the development and implementation of the new stabilization chemistries, to develop a completely new filter paper based product for Flavivirus RNA field collection and preservation. To achieve those highly Innovative and Significant goals, we propose 3 Specific Aims, to be executed over 2 years. Upon successful completion, this program will yield a product prototype that will be ready for manufacturing scale-up and international commercial deployment. The Investigators and Research Environment among the collaborating institutions (GenTegra, ATCC, and Ahlstrom) are of international caliber with respect to delivering this (21st century) approach to paper-based biosample collection. It should be noted that, although this SBIR is purely focused on Flavivirus, the technology may be generally applicable to ambient temperature collection and transport of all RNA viruses in animals and man.